Meta-Analysis of Variations in Association between APOE ɛ4 and Alzheimer’s Disease and Related Dementias Across Hispanic Regions of Origin
Open accessAbstract
Background: Emerging research has shown racial and ethnic variations in the magnitude of association between the apolipoprotein ɛ4 (APOE ɛ4) allele and the risk of developing Alzheimer’s disease and related dementias (ADRD). Studies researching this association among Hispanic groups within and outside of the United States have produced inconsistent results. Objective: To examine the association between the APOE ɛ4 allele and the risk of developing ADRD in global Hispanic populations from different ethnic regions of origin. Methods: PubMed, Embase, Scopus, and PsycInfo were searched for studies relating to Hispanic/Latin American origin, APOE ɛ4, and ADRD. Odds ratios (OR) of ADRD risk for individuals with APOE ɛ4 versus those without APOE ɛ4 were extracted and calculated using random effects analysis. Results: 20 eligible studies represented Caribbean Hispanic, Mexican, South American, Spanish, and Cuban groups. Overall, APOE ɛ4 was significantly associated with increased risk of ADRD (Odds Ratio [OR] 3.80, 95% CI: 2.38–6.07). The association was only significant in the South American (OR: 4.61, 95% CI: 2.74–7.75) subgroup. Conclusion: There was an association between APOE ɛ4 and increased ADRD risk for the South American subgroup. The strength of this association varied across Hispanic subgroups. Data is limited with more studies especially needed for adjusted analysis on Spanish, Central American, Cuban Hispanic, and Caribbean Hispanic groups. Results suggest additional environmental or genetic risk factors are associated with ethnic variations.
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The degree of risk and protection afforded by E4 and E2 respectively vary according to ancestry.
“First, the degree of risk and protection afforded by E4 and E2 respectively vary according to ancestry1,59–62.”
From APOE4 to APOE2 allelic switching in mice improves Alzheimer’s disease-related metabolic signatures, neuropathology and cognition (2025) · cites this paper as [60]
The Discussion (page unavailable) reports that the association between APOE ε4 and dementia risk varies across Hispanic groups and discusses genetic ancestry as a possible explanation. The Results (page unavailable) say the analysis focused on ε4 carriers; although ε2 genotypes are listed, the paper does not establish that ε2’s protective effect varies by ancestry. (LLM, conf=0.90)
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- Authors
- Huggins, L. K. L., Min, S. H., Kaplan, S., Wei, J., Welsh-Bohmer, K., & Xu, H.
- Affiliations
- Duke University (US)
- Columbia University (US)
- Duke Medical Center (US)
- University of South Carolina (US)
- Corresponding author
- Huggins, Lenique K.L.
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2023-05-30
- Volume
- 93
- Issue
- 3
- Pages
- 1095-1109
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC10441171
- OpenAlex
- W4376116593
- Cited by
- 18
- References
- 50
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 5 · 2023: 1
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Alzheimer's Association
- National Institute on Aging (P30AG072958)
- National Institute on Minority Health and Health Disparities (U54MD012530)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- APOE ε4, Alzheimer's disease and related dementias
- MeSH terms
- Alzheimer Disease, Dementia, Genotype, Hispanic or Latino, Humans, Racial Groups, Apolipoprotein E4
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